Filtration in organ perfusion apparatus

ABSTRACT

A filter for filtering perfusate is integrated with an exterior portion of an organ container. The filter may be used in an apparatus for perfusing an organ. The perfusion apparatus may include an organ container configured to contain an organ, the filter integrated with an exterior portion of the organ container, and another filter. At least the filter integrated with an exterior portion of the organ container may be provided in a sterilized disposable kit.

BACKGROUND

Related technical fields include organ and tissue perfusion apparatusesthat are capable of sustaining and/or restoring viability of organs ortissue and preserving organs or tissue for storage and/or transport, andmore particularly that include filters for filtering perfusate.

It is known to perfuse an organ or tissue with a perfusate in order tomaintain and sustain the organ or tissue ex vivo. The perfusate usuallycontains additives and/or nutrients to help maintain the organ ortissue. The perfusate enters into the organ, for example through a bloodvessel, and exits the organ through, for example, another blood vesselor other routes. As a result, the perfusate that has passed through theorgan or tissue may contain organic matter dispelled from the organ ortissue.

Known perfusion machines may have one or more filters. See, for example,U.S. Pat. No. 7,824,848 to Owen et al.

SUMMARY

In conventional perfusion machines, perfusate is often recirculated andmay lead to clogging and contamination of filters. Additionally, aproblem with integration filters (filters that stack two filteringmediums directly next to and/or in contact with one another) is thatthey limit the amount of effective filtration area of the finer filter.Accordingly, the filters may frequently require replacement and alsosterilization, along with other parts of the organ perfusion system thatcome into contact with the perfusate, for their continued function. Toreplace or resterilize a filter, the sterile environment around theorgan or tissue is compromised because the filter is removed from thefluid circuit. Removal of the filter from the fluid circuit causes abreak in the fluid circuit and exposes the perfusate in the fluidcircuit. As a result, sterility is compromised and the organ or tissuemay no longer be free from contamination. This could result in loss ofor damage to the organ or tissue.

For example, a relatively large piece of tissue may break free from anorgan during perfusion. The piece of tissue may be caught in a filterand/or cover the entire filter, if the piece of tissue is large enough,blocking the fluid circuit and thereby stopping perfusion of the organ.In this scenario, the tubing and/or organ container must be opened toremove the clogged filter and either replace the filter or clean thefilter such that perfusate may continue to move in the fluid circuit.However, when the tubing and/or organ container is opened, sterility iscompromised because the perfusate and/or the organ itself are exposed tocontamination.

A need exists for a perfusion machine that has replaceable or single-useparts, including filter(s), which come into contact with the perfusatefluid. Additionally, a need exists for disposable parts that are easy toreplace and that may be easily integrated in the perfusion machine. Forexample, a need exists for a perfusion machine that has a replaceableorgan or tissue container, filter(s), and tubing. It is preferable thatthe replaceable or single-use parts be sterilized and placed into asaleable package prior to use. Once the container, filter(s), and/ortubing are ready for use, it is desirable that the kit may be opened andthe container, filter(s), and tubing may be used with the perfusionmachine. Accordingly, there is a need for a kit that allows for thecontainer, filter(s), and tubing to be swapped in and out of a perfusionmachine with ease and without worry of comprising the sterility of theperfusion machine. Once an organ or tissue is removed from the perfusionmachine, the container, filter(s), and/or tubing may be discarded andreplaced without being used for another organ or tissue. Additionally,there is a need for a filter system that has an extended lifetime suchthat the filters do not need to be replaced during perfusion, transport,and/or storage of an organ or tissue inside the perfusion machine.

Advantages of various embodiments of the present invention include anorgan or tissue container and a filter that are integrated together toprovide a replaceable unit that improves ease of manufacturing.Additionally, the filter system and container improve the life of thefilter system because the filter system is designed to prevent cloggingfrom tissue from the organ or tissue. The container and filter may besold together as a single unit. The container and filter allow for usetogether with a single organ or tissue, or multiple organs or tissues,and may preferably be discarded before another organ or tissue isperfused in a perfusion machine. For ease of reference herein, the term“organ” will mean “organ and/or tissue” unless otherwise indicated.

According to exemplary implementations, a filter for filtering perfusateintegrated with an exterior portion of an organ container is provided.The filter may be molded monolithically with an exterior portion of theorgan container. The filter may alternatively be fastened to an exteriorportion of the organ container. For example, the filter may be fittedinto an aperture of the organ container. The filter may be disposedwithin the exterior portion of the organ container. The exterior portionof the container may be located on a bottom or side of the organcontainer. The exterior portion may be a wall of the organ container. Asused herein, the term “wall” includes bottom and/or side walls unlessotherwise indicated.

In exemplary implementations, an apparatus for perfusing an organincludes an organ container configured to contain an organ, a firstfilter integrated with an exterior portion of the organ container, and asecond filter. The second filter may be disposed downstream from thefirst filter. The exterior portion of the organ container may be a sideand/or bottom wall of the organ container. The first filter maypreferably be a coarser filter than the second filter. The second filtermay be disposed within a fluid conduit downstream of the first filter ina perfusate flow path. Further, the fluid conduit may be connected tothe first filter. A pump may be disposed between the first filter andthe second filter in the perfusate flow path. The first filter may beconfigured to block particles that would clog the fluid conduit of theperfusate flow path.

In exemplary implementations, the apparatus may include a fluid conduit,a pump, a pressure sensor, an oxygenator membrane, and a combinationbubble trap—pressure accumulator to remove bubbles and reducepulsatility from the pump. The perfusate flow path may, for example,begin at the first filter and then pass, in order, the fluid conduit,the pump, the pressure sensor, the second filter, the oxygenatormembrane and the bubble trap before returning to the organ container.Moreover, an organ may be disposed in a perfusate bath inside the organcontainer. The organ container may be configured to have an exteriorsurface in contact with a cooling medium. The organ perfusion apparatusmay have an organ supporting surface that is one of a plurality of wallsof the organ container. The first filter may be integrated with theorgan supporting surface. The apparatus may further comprise a cradledisposed within the organ container and having an organ supportingsurface configured to support an organ. The cradle may be configured tohold an amount of perfusate to form a perfusate bath around an organplaced inside the cradle.

Implementations may include a sterilized disposable kit comprising anorgan container configured to contain an organ and a first filter,configured to filter perfusate, integrated with an exterior portion ofthe organ container. The kit may also have a second filter. The firstfilter in the kit may be coarser than the second filter. Additionally,the kit may have an organ supporting surface. The organ supportingsurface may or may not be integrated with or part of the exteriorportion of the organ container.

In embodiments, a method for perfusing an organ includes filteringperfusate after it leaves the organ with a first filter integrated withan exterior portion of an organ container and filtering the perfusatewith a second filter downstream of the first filter. The method forperfusing the organ may utilize a filter for filtering perfusate that isintegrated with an exterior portion of an organ container. The filtermay, for example, be gravity fed or pump fed. A step of filtering theperfusate fluid with the first filter integrated with the exteriorportion of an organ container may be performed before filtering theperfusate fluid with the second filter.

A method of manufacturing an organ container may include forming afilter in an exterior portion of an organ container. The step of formingmay include insert molding the filter in an exterior portion of theorgan container, which organ container may be injection molded. Themethod of manufacturing an organ container may include providing afilter material, securing the filter material in an exterior portion ofthe organ container, and forming a connection on the organ container.The connection may be configured to connect with an organ perfusionapparatus.

Other advantages, benefits and features of the present invention willbecome apparent to those skilled in the art upon reading the detaileddescription of embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of an exemplary organ perfusion apparatus.

FIG. 2 is a perspective view of an assembly of disposable components ofan organ perfusion apparatus.

FIG. 3 is a view of a filter integrated with a basin of an organperfusion apparatus.

FIG. 4 is a side view of a basin of an organ perfusion apparatus.

FIG. 5 is a cross-section of a perspective view of a cradle and basin ofan organ perfusion apparatus.

DETAILED DESCRIPTION OF EMBODIMENTS

Referring to the accompanying drawings, exemplary embodiments of aperfusion apparatus, filters, and methods according to the inventionwill be described.

The following description refers to a perfusion apparatus, which may bea transport apparatus, diagnostic apparatus, and/or storage apparatusfor an organ or tissue. Although the exemplary systems and methodsaccording to this disclosure may be applicable to specific applications,the depictions and/or descriptions included in this disclosure are notintended to be limited to any specific application. Any perfusionapparatus that may advantageously include an organ or other biologicalsamples as described in an exemplary manner in this disclosure iscontemplated.

A filtering apparatus for filtering perfusate may include an organcontainer configured to connect with an organ perfusion apparatus andhaving a filter element integrated with an exterior portion of the organcontainer. An apparatus for perfusing an organ may include an organcontainer configured to contain an organ, a recirculating perfusate flowpath, a first filter integrated with an exterior portion of the organcontainer in the perfusate flow path, and a second filter in theperfusate flow path. The apparatus may further include a pump, apressure sensor, an oxygenator, and a bubble trap.

FIG. 1 is a schematic diagram of a perfusion apparatus 10 for an organ20. The organ 20 may preferably be a liver but may be any human oranimal, natural or engineered, healthy, injured or diseased organ ortissue. The apparatus includes a basin 30 in which the organ may beplaced. As shown in FIG. 2, the basin may have a lid 38 that covers thebasin so as to completely enclose the organ 20. The organ 20 may bedisposed in a perfusate bath inside the basin 30. In such aconfiguration, the basin 30 may include an organ supporting surfaceconfigured to hold the organ 20 when the organ is in the perfusate bath.Referring back to FIG. 1, the basin 30 may hold a cradle 60 (see FIG.5), which preferably includes a surface on which the organ 20 isdisposed when the organ 20 is in the apparatus 10. The basin 30 mayinclude a first filter 32 (see FIG. 3) that can function as a grossparticulate filter. The basin 30 and/or the cradle 60 are preferablyconfigured to allow a perfusate bath to form around the organ 20.

Preferably, the organ 20 may be disposed in a perfusate bath inside ofthe cradle 60. The cradle 60 may be configured to hold an amount ofperfusate to form a perfusate bath around the organ 20 placed inside thecradle 60. The perfusate bath may partially immerse the organ 20 or mayfully immerse the organ 60. The cradle 60 and basin 30 may be designedsuch that overflow from the perfusate bath in the cradle 60 is receivedinside of the basin 30, which may form a secondary bath.

The perfusate bath preferably collects in the basin 30 before it passesthrough the first filter 32. The perfusate flows through the firstfilter 32, such as by gravity or by way of pump 80. When the perfusateis gravity fed through the first filter 32, the first filter 32 may betypically located at or near a bottom portion of the basin 30 such thatgravity pushes the perfusate through the first filter 32. However, thepump 80 may apply a pressure or negative pressure (suction) to theperfusate such that the perfusate passes through the first filter 32.The pump 30 may be used in configurations in which the first filter 32is not located at or near a bottom portion of the basin 30.

The basin 30 may also include a temperature sensor 40 located in or nearthe cradle 60. The basin may include multiple temperature sensors 40,which may provide redundancy in the event of a failure and/or mayprovide temperature measurement at multiple locations. Preferably, thetemperature sensor 40 is an infrared temperature sensor. The temperaturesensor 40 is preferably disposed as close as practical to the organ 20when the organ 20 is disposed in the cradle 60 in order to improve theusefulness and accuracy of the temperature sensor 40, which preferablyprovides a temperature measurement of the perfusate that may becorrelated to a temperature of the organ 20. Alternatively oradditionally, the temperature sensor 40 may be used to directly measurethe temperature of the organ 20.

The basin 30 is preferably disposed within an insulating coolingcontainer 50 that may contain cold materials such as ice, ice water,brine or the like, or may be cooled by a cooling device such as anelectrical or gas powered cooling device. Cooling container 50 may bepermanently or removably attached to, or an integral, monolithic partof, apparatus 10. Thus, in use as shown in the Figures, the organ 20 isdisposed within the cradle 60, which is disposed within the basin 30,which is disposed within the cooling container 50. Preferably, each ofthe basin 30, cradle 60 and cooling container 50 is configured, orkeyed, to fit within its corresponding mating component in a singleorientation. The configuration of the cooling container 50, basin 30 andcradle 60 may provide a configuration that provides cooling for theorgan 20 without the contents of cooling container 50 contacting theorgan 20 or the cradle 60. The basin 30 may be configured to have anexterior surface in contact with a surface of the cooling container 50,which provides thermal communication with a cooling medium in thecooling container 50. Although the cooling container 50 is describedherein as containing ice, any suitable cooling medium can be used. Icemay be preferable due to the ease with which ice can be procured, butone of ordinary skill would understand that any suitable cooling medium,which could be an active cooling medium (such as a thermo electriccooler or a refrigerant loop) or a passive cooling medium similar to iceor ice water, or a combination thereof, may be utilized. The amount ofice, or other cooling medium, that can be placed within the coolingcontainer 50 may, for example, be determined based upon the maximum timethat cooling is likely to be provided while the organ 20 will be in theapparatus 10.

The cradle 60 may include components configured to securely restrain theorgan 20 in place. Such components may, for example, include userselectable netting that is fastened to the cradle 60. The cradle 60 mayalso have an organ supporting surface configured to support the organ20. The organ supporting surface may be a surface that is shaped toreceive the organ 20 in a shape that is complementary to the generalshape of the organ in a preferred orientation of the organ.

FIG. 2 is a perspective view of an exemplary arrangement of disposablecomponents 190 of the organ perfusion apparatus 10. The disposablecomponents 190 preferably include the basin 30, which may be configuredto contain an organ 20. The first filter 32 may be integrated with anexterior portion of the basin 30 and a second filter 34 may also beprovided. The second filter 34 may be disposed downstream from the firstfilter in a fluid conduit 72 that defines a first flow path 70. Thefluid conduit 72 may be connected to the first filter 32 and/or may beconnected to an exterior or interior portion of the basin 30.Preferably, all components of the apparatus 10 that come into contactwith perfusate and/or the organ 20 are disposable and/or easilyreplaced, most preferably as a single unit with most or all partsconnected together as shown in FIG. 2. The components of the organperfusion apparatus that are not disposable may be reused indefinitely.

The disposable components 190 of the organ perfusion apparatus 10 maypreferably be sterilized prior to use. Some or all of the disposablecomponents 190 may be provided in the form of a sterilized disposablekit. For example, the sterilized disposable kit may comprise the basin30, the first filter 32, and the second filter 34. The sterilizeddisposable kit may further include the organ supporting surface, and/orother parts of the disposable components 190 such as the conduits,oxygenator membrane, and bubble trap. The disposable components 190 arepreferably manufactured in a clean environment and sterilized as acompleted saleable unit with seal packing functioning as a sterilebarrier. The packing protects the sterilized, disposable components frombeing contaminated. The disposable components 190 may be sterilizedwhile in the package. Once the components 190 are ready for use, thepackage may be opened and the components 190 may be used with the organperfusion apparatus 10. This allows the sterilized, disposablecomponents to be “single-use” components. That is, once an organ 20 isremoved from the basin 70, the sterilized, disposable components 190 maybe discarded and replaced without being used for another organ.Accordingly, the organ perfusion apparatus 10 maintains strict sterilityand prevents contamination of an organ 20 being perfused, transported,and/or stored in the organ perfusion apparatus 10.

Such a kit may include packaging such as plastic or shrink wrappackaging containing some or all of the components that come intocontact with an organ 20 and/or perfusate. In embodiments, the tubing,filter, oxygenator and bubble trap are packaged together, and the cradleand basin are packaged individually or together, and optionally togetherwith the tubing, filter, oxygenator and bubble trap in a mannerpreconfigured to be placed into a flow path arrangement offixed-location parts in apparatus 10, for example as shown in FIG. 2.

After passing through the filter 32, the perfusate flows along a firstflow path 70 that includes a suitable fluid conduit 72, such as flexibleor rigid tubing, passing a pump 80, a pressure sensor 90, a secondfilter 34, an oxygenator 100, and a bubble trap 110, each of which isdiscussed below. The second filter 34 may be gravity fed or pump fedsimilar to the first filter 32.

The first filter 32 is preferably a coarser filter than the secondfilter 34 such that the first filter 32 preferably blocks relativelylarger particles and the second filter 34 preferably blocks relativelysmaller particles. Accordingly, the mesh, membrane, or other structureor material used for the first and second filters 32, 34 may bedifferent and finer in the second filter 34 than in the first filter 32.In some embodiments, the first filter 32 can be configured to filtercertain types of organ matter while the second filter 34 is configuredto filter different types of organ matter. The first filter 32 may be arelatively large filter compared to the second filter 34. The firstfilter 32 preferably provides filtration that is fine enough to at leastblock particles that would clog the fluid conduit 72 of the perfusateflow path 70 (e.g., particles that are larger than an interior diameterof the flow path) while the first filter 32 itself does not becomeclogged. Finer filtration may also be provided in the first filter.

For example, the first filter 32 may be a screen filter and the secondfilter 34 may be a cartridge or capsule filter. The first filter 32 maypreferably be made of a monofilament fabric and may be made of apolymer, metallic, or composite material. The first filter 32 may be anyshape, including cylindrical or pleated, or a non-woven depth filter,preferably round and flat, or insert molded or potted, and have adiameter between 0.1 to 20 inches, preferably between 1 to 10 inches,and most preferably between 4 to 5 inches. The first filter may have anaverage opening size of 10 to 10,000 microns and preferably 100 to 3,000microns. Such a coarse filter may be provided to prevent largeparticles, which may include byproducts of the organ or of the organbeing removed from the donor, from entering and clogging fluid paths ofthe apparatus 10.

The apparatus 10 may include upstream tubing and peristaltic pumpsegment tubing that may be any diameter. For example, upstream tubingthat is located between the first filter 32 and the bubble trap 110 maybe nominally between 0.03 to 1 inch inner diameter, preferably 0.1 to0.5 inches inner diameter, and more preferably between 0.35 to 0.4inches inner diameter. For example, the upstream tubing may be about0.375 inches in inner diameter with a cross sectional area of 0.110square inch. The upstream tubing is preferably clear, with a controlledwall thickness and controlled stiffness (durometer) preferably aboutShore-A-40. This tubing may preferably be PVC but can be made of any TPEor thermoplastic, medical grade material. For example, peristaltic pumpsegment tubing may be nominally between 0.01 to 1 inch inner diameter,preferably 0.1 to 0.5 inches inner diameter, and more preferably 0.3 to0.325 inches inner diameter. For example, the peristaltic pump segmenttubing may be about 0.312 in inner diameter and is a thermoplastic setsuch as silicone but can be any other plastic material such as PVC or aTPE. This material is also a controlled durometer and wall thickness.With a 4.5 inch diameter filter having a cross sectional surface area of15.9 square inches, the ratio of cross sectional areas between the firstfilter 32 and the upstream tubing is 144:1. However, the ratio of crosssectional area between the first filter 32 and the upstream tubing maybe any ratio such that the first filter 32 prevents pieces of tissuefrom clogging the upstream tubing.

The first filter 32 may be an integral part of the basin 30 or the firstfilter may be disposed elsewhere in the first flow path 70 downstream ofthe basin 30. The first filter 32 may also be a separate componentdisposed on, inside or outside of the basin 30 or disposed within thefluid conduit 72.

The second filter 34 may be any filter capable of filtering perfusate.For example, the second filter 34 may be a compact, pleated filterelement that is integrally sealed into a housing. The housing may be,for example, polypropylene or any other suitable polymer or compositematerial. The filter element and housing may be thermally bonded into aself-contained unit to form a cartridge and capsule. The second filter34 may preferably have a filter surface area of 0.25 ft² to 0.75² andmore preferably about 0.45 ft² to 0.55 ft², such as 0.5 ft².

The first filter 32 may be made integral with the basin 30 in numerousways. For example, the first filter 32 may be molded into or as part ofa molded basin 30. Examples of molding techniques include injectionmolding, cast molding, compression molding, and other molding techniquesappreciated by one skilled in the art. The basin 30 may be molded aroundthe first filter 32 such that the basin 30 is integrated with the firstfilter 32 around a perimeter edge or circumference of the first filter32. The first filter 32 may be placed in a mold cavity or die andsubsequently have a resin, polymer, or metallic material formed aroundthe first filter 32 such that the first filter 32 is connected to thebasin 30. The first filter 32 may alternatively be inserted and held inplace with a separate, molded, retaining feature such as a simple ringor snap ring. The first filter 32 may also be fastened to the basin 30in other ways. For example, the first filter 32 may be fastened bythreaded (such as screws, nuts and bolts) or non-threaded fasteners,adhesives, hook-and-loop fasteners, or other fastening techniquesappreciated by one skilled in the art. Moreover, the first filter 32 maybe fitted into an aperture of the basin 30. The first filter 32 may bedimensioned such that the aperture within the basin is slightly larger,exactly the same size, or slightly smaller than the dimensions of thefirst filter 32. The first filter 32 may then be pushed and/or placedinside the aperture with enough force to fit the first filter 32securely within the basin 30. The first filter 32 may, for example, bepress-fitted, snap-fitted, or screwed into the aperture of the basin 30.Additional ways of securing the first filter 32 into the basin mayemploy hooks, tabs, covers, and/or other securing devices appreciated bythose skilled in the art. The first filter 32 may also be disposedinside of an exterior portion of the basin 30. For example, the firstfilter 32 may be disposed inside a wall of the basin 30 such that theouter circumference or periphery of the first filter 32 is between twosurfaces of the wall (as shown in FIG. 3).

The exterior portion of the basin 30 may be a wall of the basin or maybe another structure attached to the basin 30 or a part of the basin 30.For example, the exterior portion may be a structure configuredspecifically to hold the first filter 32. The first filter 32 may bedetachable from the basin 30 or may be permanently integrated with thebasin 30. The exterior portion may also be other structure that has anexterior surface facing an outside of the basin 30. The exterior portionof the basin 30 may be located on a bottom of the basin 30. The exteriorportion of the basin 30 may be the bottommost structure of the basin 30and/or it may be an intermediate structure of the basin 30. The exteriorportion may be a wall of the basin 30. Additionally, as discussed above,the basin 30 may have an organ supporting surface upon which the organ20 is placed and this organ supporting surface may be an inner surfaceof the basin with which the first filter is integrated.

FIG. 3 shows an example of the first filter 32 integrated with anexterior portion of the basin 30. FIG. 4 shows an extended portion 42 ofthe basin 30. As illustrated, the extended portion 42 generally has acylindrical or other shape and is located on a bottom of the basin 30.The extended portion 42 may be in the shape of a cup on the bottom ofthe basin 30. The extended portion 42 may have an end surface that isangled (e.g., substantially perpendicular) relative to the length of theextended portion 42. The end surface may be partially or completelyangled such that all or part of the end surface of the extended portion42 is not perpendicular to a side wall of the extended portion 42. Oneside of the extended portion 42 may be open and the other end of theextended portion 42 may be closed or sealed. The extended portion 42 maybe located in a substantially center area or at a side of a bottom ofthe basin 30. A width or diameter of the extended portion 42 maypreferably be larger than the height or length of the extended portion42. The extended portion 42 may be integral with the basin 30 and may bemolded monolithically with or attached to the basin. The extendedportion 42 may define a secondary chamber between the first filter 32and the fluid conduit 72. Various manufacturing techniques may be usedto form the extended portion 42 of the basin 30. The extended portion 42preferably has a port 44 that is connected to the fluid conduit 72 (notshown in FIG. 4). This configuration and structure of the first filter32 and basin 30 may allow for organ matter that is larger than adiameter of the fluid conduit 72 to be filtered out by the first filter32 without clogging the first filter 32 due to the diameter of the firstfilter being relatively larger than the diameter of the fluid conduit72.

The first flow path 70 may also include a pump 80. The pump 80 may beany pump that is suitable in connection with perfusing of organs.Examples of suitable pumps may include hand operated pumps, centrifugalpumps and roller pumps. If a roller pump is included, the roller pumpmay include a single channel or flow path (where only one tube iscompressed by the rollers) or the roller pump may include multiplechannels or flow paths (where multiple tubes are compressed by therollers). If multiple, parallel channels or flow paths are included, therollers may preferably be disposed out of phase or offset so that pulsescreated by the rollers are out of phase, which may result in a fluidflow out of the roller pump that is relatively less pulsatile than wouldbe the case with a single roller. Such a multiple channel roller pumpmay achieve a constant flow rate or a minimally pulsatile flow rate,which may be advantageous depending on the other components in the flowpath and/or the type of organ being perfused. The pump 80 is shown asbeing disposed between the first filter 32 and the second filter 34, butmay be disposed anywhere along the flow path. For example, the pump 80may be disposed downstream of both the first filter 32 and the secondfilter 34.

The flow path 70 may include a pressure sensor 90. The pressure sensor90 may preferably be disposed after the outlet of the pump 80 in orderto be used to monitor and/or control the pressure produced at the outletof the pump by way of a suitable controller, such as a computer,microprocessor, central processing unit, and/or workstation. Thepressure sensor 90 may provide continuous or periodic monitoring ofpressure.

The flow path 70 may include an oxygenator 100 such as an oxygenatormembrane or body to provide oxygenation to the perfusate. Oxygen may beprovided to the oxygenator 100 by any suitable means. Suitable oxygensources may provide pure oxygen or mixed gases such as air. The gas maybe compressed, such as in a high-pressure cylinder, liquefied as wouldbe stored in a dewar, or drawn from the surrounding atmosphere.Preferably, the oxygen may be provided by way of an oxygen generator,which may be separate from the apparatus 10 or integral to the apparatus10. Oxygen may be generated through any suitable means, some examples ofwhich include through pressure swing adsorption using a molecular sieve,through a ceramic oxygen generator (a solid state oxygen pump) orthrough decomposition of water.

The flow path 70 may include a bubble trap 110. The bubble trap 110preferably separates gas bubbles that may be entrained in the perfusateflow and prevents such bubbles from continuing downstream and enteringthe organ 20. The bubble trap 110 may also function as an accumulatorthat reduces or eliminates pulsatility of the perfusate flow. The bubbletrap 110 may include a volume of gas, initially or through theaccumulation of bubbles, such that pressure fluctuations in theperfusate are dampened or eliminated.

The bubble trap 110 may include a vent that allows purging of gas duringstart up or a purging process. The vent may be connected to or part ofpurge flow path 140 (which is discussed in detail below). The vent ispreferably open during a start up process so that any air or other gasmay be purged from the perfusate path 70. Once the gas is purged fromthe perfusate path 70, the vent may preferably be closed. The vent maybe closed manually or may be closed automatically by way of a suitablecontroller.

The bubble trap 110 may include a level sensor 112 to ensure that atleast a predetermined air space above the fluid level is maintained. Thelevel sensor 112 may, for example, include a float that includes amagnet that interacts with Hall Effect sensors in the transporter. Alevel sensor 112 may optionally be used during the purging process todetermine when the purging is complete and/or may be used to determinewhen the purging process needs to be repeated, which may happen afterbubbles have been trapped in the bubble trap 110. Also, through use ofthe level sensor 112 and the vent, the accumulator function of thebubble trap can be tuned to account for differing amplitudes andfrequencies of pulsatility in the perfusate flow.

The bubble trap 110 may have any number of outlets, as needed for agiven application of the perfusion apparatus. In FIG. 1, three outletsare shown connected to three different flow paths, which may beparticularly suited for perfusion of a liver. When perfusing a liver,the three paths preferably include portal flow path 120 connected to theportal vein of a liver, hepatic flow path 130 connected to the hepaticartery of a liver, and bypass flow path 140 that provides a return pathto the basin 30.

As shown in FIG. 1, the portal flow path 120 and hepatic flow path 130may optionally include similar or different components such as valves122, 132; bubble sensors 124, 134; flow sensors 126, 136; flow controlclamps 127, 137; and pressure sensors 128, 138. Each similar componentmay function in a similar manner, and such pairs of components mayoptionally be structurally and/or functionally identical to reducemanufacturing costs.

Valves 122, 132 may be pinch valves that function to squeeze tubing andreduce or shut off flow, but any suitable valve may be used. Pinchvalves may be advantageous because in normal usage they do not come intocontact with the perfusate and therefore do not require replacementand/or cleaning after use.

Preferably, the bubble sensors 124, 134 are ultrasonic sensors disposedaround tubing, although any suitable sensor may be used. Similar topinch valves, ultrasonic sensors may be advantageous because in normalusage they do not come into contact with the perfusate and therefore donot require replacement and/or cleaning after use. Instead, ultrasonicsensors can be disposed in contact with, adjacent to or around anexternal surface of tubing in order to sense bubbles.

Flow control clamps 127, 137 are optional and may be used to fine-tunethe flow rate in one or both of portal flow path 120 and hepatic flowpath 130. Preferably, the organ provides self-regulation to control anamount of flow that exits the bubble trap 110 and is divided between theportal flow path 120 and the hepatic flow path 130. In such selfregulated flow, pressure sensors 128, 138 provide overpressuremonitoring. In the event that pressure delivered to the organ in eitheror both of the portal flow path 120 or the hepatic flow path 130 exceedsa predetermined threshold, the apparatus 10 can automatically stopand/or reduce the flow rate provided by the pump 80 to prevent damage tothe organ. In addition or alternatively, the pressure sensors 128, 138may be used to generate warning signals to the user and/or to anappropriate controller as pressures approach the predeterminedthreshold.

After exiting one or both of the portal flow path 120 and hepatic flowpath 130, pefusate flows through the organ and returns to the basin 30to form an organ bath.

Bypass flow path 140 may include a valve 142, and/or sensors such asoxygen sensor 144 and pH sensor 146. Preferably, the valve 142 is apinch valve and may be of similar configuration to valves 122 and 132,but any suitable valve may be used. The oxygen sensor 144 and the pHsensor 146 may be used to determine the state of the perfusate.Preferably, the bypass flow path 140 is only used during a purging orpriming process, although it may also be used during perfusion,preferably continuously, to monitor perfusate properties in real time.

The organ perfusion apparatus 10 may also include an accelerometer 150.Preferably the accelerometer 150 is a three-axis accelerometer, althoughmultiple single axis accelerometers may be used to the same effect. Theaccelerometer 150 may be used to continuously or periodically monitorand/or record the state of the apparatus 10. Monitoring may includemonitoring for excessive shocks as well as attitude (e.g., pitch andyaw) of the apparatus 10. By implementing such monitoring, misuse orpotentially inappropriate conditions of the apparatus 10 can be detectedand recorded.

The apparatus 10 may include storage compartments for items other thanthe organ 20. For example, the apparatus 10 may include a documentcompartment 160 to store documents and/or charts related to the organ20. Also, the apparatus 10 may include one or more sample compartment170. The sample compartment 170 may be configured, for example, to storefluid and/or tissue samples. The sample compartment 170 may beadvantageously disposed near the cooling container 50 to providecooling, which may be similar or equivalent to the cooling provided forthe organ 20.

The apparatus 10 may include one or more tamper evident closures 180. Atamper evident closure 180 may be used to alert a user that theapparatus 10 has been opened at an unauthorized time and/or locationand/or by an unauthorized person. Evidence of tampering may alert theuser to perform additional testing, screening, or the like before usingthe organ 20 and/or the apparatus 10.

What has been described and illustrated herein are preferred embodimentsof the invention along with some variations. The descriptions andfigures used herein are set forth by way of illustration only and arenot meant as limitations. Those skilled in the art will recognize thatmany variations are possible within the spirit and scope of theinvention.

What is claimed is:
 1. A filtering apparatus for filtering perfusate,comprising: an organ container having a connection configured to connectwith an organ perfusion apparatus; and a filter element integrated withan exterior portion of the organ container.
 2. The filter of claim 1,wherein the filter element is molded into the exterior portion of theorgan container.
 3. The filter of claim 1, wherein the exterior portionis located on a bottom of the organ container.
 4. The filter of claim 1,wherein the filter element is fitted into an aperture of the exteriorportion of the organ container.
 5. The filter of claim 1, wherein thefilter element is disposed in the exterior portion of the organcontainer such that an outer circumference or periphery of the filterelement is between two surfaces of the exterior portion of the organcontainer.
 6. The filter of claim 1, wherein the filter element isdetachable from the organ container.
 7. The filter of claim 1, whereinthe filter element is a screen filter.
 8. The filter of claim 1, whereinthe filter element has an average opening size of 1,000 microns to 3,000microns.
 9. An apparatus for perfusing an organ, comprising: an organcontainer configured to contain an organ; a recirculating perfusate flowpath; a first filter integrated with an exterior portion of the organcontainer in the perfusate flow path; and a second filter in theperfusate flow path.
 10. The apparatus of claim 9, wherein the secondfilter is disposed downstream of the first filter in the perfusate flowpath.
 11. The apparatus of claim 9, wherein the first filter is acoarser filter than the second filter.
 12. The apparatus of claim 9,further comprising a cradle disposed within the organ container, thecradle having an organ supporting surface configured to support anorgan.
 13. The apparatus of claim 12, wherein the organ container isconfigured to hold perfusate to form a perfusate bath around an organplaced in the cradle.
 14. The apparatus of claim 9, wherein the secondfilter is disposed within a fluid conduit downstream of the firstfilter.
 15. The apparatus of claim 14, wherein the fluid conduit is influid communication with the first filter.
 16. The apparatus of claim 9,further comprising: a pump disposed between the first filter and thesecond filter in a perfusate flow path.
 17. The apparatus of claim 9,wherein the first filter is sized to prevent particles from blocking thefirst filter.
 18. The apparatus of claim 9, further comprising: a pump;a pressure sensor; an oxygenator; and a combo bubble trap.
 19. Theapparatus of claim 18, wherein the perfusate flow path comprises aconduit that begins at the first filter and then passes, in order, thepump, the pressure sensor, the second filter, the oxygenator and thebubble trap before returning to the organ container.
 20. The apparatusof claim 9, wherein a diameter of the first filter is between about 4and 5 inches.
 21. The apparatus of claim 14, wherein the first filterhas an area that is at least two times a cross-sectional area of thefluid conduit.
 22. The apparatus of claim 9, wherein the organ containercomprises an extended portion at the bottom of the organ container andforming a secondary chamber between the first filter and a fluidconduit.
 23. The apparatus of claim 9, wherein the first filter is ascreen filter.
 24. The apparatus of claim 9, wherein the second filteris a cartridge or capsule filter.
 25. The apparatus of claim 9, whereina filter surface area of the second filter is about 0.5 ft².
 26. Theapparatus of claim 9, wherein the first filter has an average meshopening size of 100 to 1,000 microns.
 27. A sterilized disposable kit,comprising: sterilized packaging containing: a sterilized organcontainer configured to contain an organ, the sterilized organ containerincluding a sterilized first filter configured to filter perfusate andintegrated with an exterior portion of the organ container.
 28. The kitof claim 27, further comprising a sterilized second filter disposedinside of the sterilized packaging.
 29. The kit of claim 28, wherein thefirst filter is coarser than the second filter.
 30. The kit of claim 29,further comprising a fluid conduit, an oxygenator, and a bubble trap,contained in the sterilized packaging.
 31. A method of perfusing anorgan, comprising: (a) perfusing an organ with a perfusate in an organcontainer; (b) filtering the perfusate after it leaves the organ with afirst filter integrated with an exterior portion of the organ container;(c) filtering the perfusate fluid with a second filter downstream of thefirst filter; and (d) returning the perfusate to repeat steps (a)through (c).
 32. The method of claim 31, wherein the first filter is acoarser filter than the second filter.
 33. A method of manufacturing anorgan container, comprising: providing a filter material; securing thefilter material in an exterior portion of the organ container; andforming on the organ container a connection configured to connect withan organ perfusion apparatus.
 34. The method of claim 33, wherein theorgan container is formed by injection molding.
 35. The method of claim34, wherein the organ container is injection molded around the filtermaterial.